1. Field of the Invention
This invention relates generally to cells that are permissive for hepatitis C virus (HCV) replication, and methods and materials for making and using them.
2. Related Art
Adaptive mutations in the HCV non-structural proteins that increase RNA replication, and the frequency of Huh-7 cells supporting detectable levels of replication, have been identified previously. (Blight, K. J. et al, Science 290:1972-1974, 2000; Guo, J. T. et al., J. Virol. 75:8516-8523, 2001; Kreiger, N. et al., J. Virol. 75:4614-4624, 2001; Lohmann, V. et al., J. Virol. 75:1437-1449, 2001). In particular, replacement of the Serine residue with Isoleucine at position 2204 in NS5A permits HCV replication in ˜10% of transfected Huh-7 cells (a 20,000-fold improvement over non-mutated HCV) and increases replication to a level sufficient for the detection of HCV RNA early after transfection. (Blight et al., 2000). The low frequency of Huh-7 cells supporting HCV replication suggests that the cellular environment may be a major determinant of HCV replication efficiency.